Beta-lactam Intermittent Versus Continuous Infusion and Combination Antibiotic Therapy in Sepsis

Launched by ASSISTANCE PUBLIQUE - HÔPITAUX DE PARIS · Dec 26, 2022

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ClinConnect Summary

This clinical trial is studying different ways to give antibiotics to patients with sepsis, a serious infection that can lead to organ failure. Specifically, it compares two methods of delivering a type of antibiotic called beta-lactams: one where the medicine is given all at once (continuous infusion) and another where it is given in smaller doses over time (intermittent infusion). The trial also looks at whether combining antibiotics works better than using just one. It is open to adults who have been diagnosed with hospital-acquired sepsis or septic shock within the last 24 hours and who have certain risk factors for infections caused by drug-resistant bacteria.

To participate, patients need to be at least 18 years old and expected to stay in the ICU for more than three days. They should have specific risk factors, like recent antibiotic use or a long hospital stay. Participants can expect to receive the assigned treatment while being closely monitored for their health during the trial. It's important to know that there are strict eligibility criteria to ensure safety, and patients with certain allergies or medical conditions cannot take part in the study.

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Eligibility criteria

• Inclusion Criteria:
• • Adults (≥ 18 years)
• * Hospital-acquired sepsis (according to sepsis 3.0 definitions) :
• • Patient hospitalized for more than 48 hours OR Patient discharged less than 48 hours ago
• • AND sepsis diagnosed within the last 24 hours
• * One of the following risk factors for gram negative multidrug resistant pathogens:
• • Prior intravenous antibiotic use within 7 days prior to sepsis onset with the exception of antibiotic effective only against Gram-positive bacteria, penicillin A and macrolides
• • Prolonged hospital stay (≥ 15 days of hospitalization) within 3 months prior to sepsis onset Prolonged mechanical ventilation (≥ 5 days on mechanical ventilation) within 3 months prior to sepsis onset
• • Patients with indwelling devices (dialysis access lines, intravascular lines, urinary catheter, endotracheal or tracheostomy tube, gastrostomy or jejunostomy feeding tube)
• • Patients known to be infected, colonized or carriers of MDR gram negative bacteria within 3 months prior to sepsis onset
• • Exposure to an antibiotic (amoxicillin-clavulanic acid, C2G, C3G, fluoroquinolones) within 3 months prior to sepsis onset
• • A trip abroad to known geographical areas at risk (in particular the Indian subcontinent, South-East Asia, the Middle East and North Africa, the Mediterranean Basin) within 3 months prior to sepsis onset
• • A functional or organic abnormality of the urinary tract in case of urinary tract infection.
• • Appropriate bacteriological sampling performed before starting antimicrobial therapy
• • Expected stay in ICU of more than 3 days
• Exclusion Criteria:
• • A priori known resistance to all the proposed beta-lactams or to amikacin
• • Need for extrarenal treatment at inclusion according to the criteria of Gaudry et al.
• • Known hypersensitivity to ceftazidime, piperacillin-tazobactam, cefepime, meropenem, ceftazidime-avibactam, ceftazolane-avibactam or to any of the excipients included in the corresponding pharmaceutical drugs,
• • Known hypersensitivity to any cephalosporin antibacterial agent,
• • Know hypersentitivity to any penem antibacterial agent,
• • Severe known hypersensitivity (eg, anaphylactic reaction, severe skin reaction) to any other beta-lactam antibiotic (eg, penicillins or monobactam ) or to any of its excipients.
• • Known contraindication to the aminoglycoside family including
• • Hypersensitivity to the active substance, to any aminoglycoside antibacterial agent or to any of the excipients included in the corresponding pharmaceutical drugs,
• • Cirrhosis of grades B and C according to the Child-Pugh classification.
• • Myasthenia gravis.
• • Simultaneous administration of another aminoglycoside
• • Association with ataluren
• • Non-complicated urinary tract infection (corresponding to a positive ECBU not responsible for sepsis)
• • Bone marrow transplant or chemotherapy-induced neutropenia
• • Infections for which long-term antibiotic treatment \> 8 days is strongly recommended (i.e., infective endocarditis, osteoarticular infections, anterior mediastinitis after cardiac surgery, hepatic or cerebral abscesses, chronic prostatitis for instance
• • Presence of antibiotic therapyfor the new sepsis before randomisation: (\> 2 doses of antibiotics or \> 16h for continuous infusion
• • Limitation of life support (comfort care applied only) at the time of screening
• • Enrolment to another interventional drug study
• • Pregnancy or breastfeeding
• • Subject deprived of freedom, subject under a legal protective measure
• • Non affiliation to any health insurance system
• • Refusal to participate to the study (patient or legal representative or family member or close relative if present)